A new RCT published in the Journal of Perinatology suggests that a midline head position with head elevated at 30 degrees might reduce severe intracranial hemorrhage. (Kochan M, et al. Elevated midline head positioning of extremely low birth weight infants: effects on cardiopulmonary function and the incidence of periventricular-intraventricular hemorrhage. J Perinatol. 2018). The authors randomized 180 babies of less than 1 kg birth weight to either prone positioning with the head turned every 4 hours, or supine, with the head maintained in the midline, and placed on a wedge-shaped frame inside their incubator with a slope of 30 degrees.
They note in the introduction that maintaining the head in the midline has become part of some quality control guidelines for reduction of IVH. Even though that is true, I am not aware of any prospective trials that show an impact of head position on IVH, and the authors of this study do not quote any. There are several physiologic type studies that have examined the very short term consequences of different head position, but none have demonstrated that those changes are either persistent over 2 to 4 days, or aetiologically associated with intracranial bleeding. The Cochrane review of the issue (from 2017) found 2 studies that compared supine midline positioning to supine lateral head positioning (n=110 total), and found no evidence that there was an impact on the frequency or severity of IVH.
This trial report leaves several unanswered questions, partly because it doesn’t follow CONSORT guidelines. Specifically regarding randomization procedures, the randomization was “using a block randomization table” and was “performed using SAS V9.4” CONSORT guidelines do require the method of generation of the randomization sequence, but also require a description of the mechanisms of allocation concealment, and the implementation of the whole process.
The way it is reported leaves open the possibility that investigators knew which group the next patient would be enrolled in. There are also a few other things that are unclear, the report notes that there were 60 infants who were twins, and that they were randomized individually, but then in the final two groups there were only 29 twins. This seems to imply that infants were randomized, but then did not participate in the study, the major exclusion factor being that an investigator was not available to do the initial ultrasound, which was done immediately after the baby was in the randomized position. That also implies that once a baby was randomized and placed in the position, the ultrasonographers availability would be evaluated. This also leaves a chance for unconscious bias in enrolment.
The primary outcome variable of the study was “the incidence of PIVH”, (that is periventricular and intraventricular hemorrhage) although it is not named as being the primary outcome variable. The purpose of the study is described as being to determine whether the body position would “decrease in the incidence of PIVH” [sic] and the sample size was calculated based on a hypothesized decrease in PIVH from 40% to 20%.
I can’t find a registration record for this trial, which would list the primary outcome variable, and there is no registration mentioned in the manuscript.
Amazingly enough, there is no presentation in the publication of a statistical analysis of the primary outcome variable, in the abstract the primary outcome variable is not mentioned at all.
So here is the analysis of the primary outcome variable: there were 34 infants with PIVH in the head elevated group, and 31 infants with PIVH in the prone group; 38% vs 34%, a difference of 3.3% (95% confidence intervals -11%, +18%). This is clearly a result that could have arisen by chance, in other words this is a negative trial, and secondary outcomes that might be different between groups can only be hypothesis-generating.
Unfortunately the abstract only refers to 2 secondary outcomes, and doesn’t mention the primary. As there is no registration record or published protocol we do not know if those secondary outcomes were chosen after the results were examined or before. Those secondary outcomes are arguably more clinically important than the primary outcome; “grade 4” hemorrhage and survival. Both of those were slightly better in the head elevated group.
The incidence of “grade 3 and grade 4” hemorrhage in the prone/flat babies was 20%, and in the head elevated babies was 12.2%. I put those together to compare to recent data from the Canadian Neonatal Network, for which in babies less than 1kg the incidence of grade 3 and 4 hemorrhages is around 10%.
Also of interest, all but one of the babies in this study each group of this study were intubated on day 1, and the authors never state if there was a minimum weight for eligible babies.
I think it is a real shame to take the time and effort to do a worthwhile trial like this, and not register it, not make the protocol available (either as supplemental information with the publication or by publishing it), and not report it according to CONSORT guidelines.
I would say that the results do show quite a high incidence of serious hemorrhages in the flat/prone group, and if the random allocation was indeed concealed, the trend to fewer serious hemorrhages in the elevated/supine/midline group is something that warrants further investigation.
Keeping the baby’s head midline, supine and 30 degree elevated positioning means that the infant can’t be prone, and they can’t go in kangaroo, at least not the way it is normally done. So we will need to know if this is a real effect, and if so which part of the positioning is important, elevation, supine positioning, or head midline. Many babies in the category of less than 1000g birthweight are at quite low risk of serious hemorrhage, larger inborn babies who have completed steroids, and especially those who are never intubated, uncommonly develop PVHI. A study in babies selected for higher risk would need fewer numbers, and might be easier to get completed in a reasonable time. The intervention is cheap so keeping organizational costs to a minimum might make a trial with a high potential impact, at relatively low expense.